It is known that ACAT is an enzyme which catalyzes synthesis of cholesterol esters from fatty acid acyl-coenzyme A and cholesterol, and esterification of cholesterol in the living body is effected mostly by the function of ACAT (A. A. Spector et al., Prog. Lipid Res., vol.18, pp.31-53 (1979)).
In addition, since increase in the ACAT activity has been found in experimentally prepared atherosclerotic lesions, a relationship between the accumulation of cholesterol esters and the ACAT activity in atherosclerotic lesions has been indicated (St. Clair et al., Circ. Res., vol.27, pp.213-225 (1970); St. Clair et al., Prog. Cardiovasc. Dis., vol.26, pp.109-132 (1983); P. M. Kinnuen et al., Biochemistry, vol.27, pp.7344-7350 (1988)).
On the other hand, with regard to the absorption of dietary cholesterol, it is known that free cholesterol in the intestinal tract is esterificated in the small intestine mucous membrane and then secreted as chylomicron into the lymphatic duct, and ACAT located in the small intestine mucous membrane is greatly concerned in the esterification of cholesterol (K. E. Sucklinget et al., J. Lipid Res., vol.26, pp.647-671 (1985); J. G. Heider et al., J. Lipid Res., vol.34, pp.176-183 (1983)).
Thus, it seems that an ACAT inhibitor can inhibit formation and progress of atherosclerosis by inhibiting accumulation of cholesterol esters in atherosclerotic lesions and also can inhibit absorption of cholesterol in the small intestine mucous membrane.
Examples of prior art ACAT inhibitors include substituted urea derivatives disclosed in U.S. Pat. No. 4,623,662 and anilide derivatives disclosed in JP-A-60-41655 and JP-A-63-253060, though their functions are not sufficient enough.
Though compounds similar to the compound of the present invention have been disclosed in JP-A-54-39028 and U.S. Pat. No. 3,878,248, they have no strong ACAT inhibiting activities.
A primary object of the present invention is to provide a compound having a potent ACAT inhibiting activity.